The successful development of a tracer kinetic model and an operational equation for 2-fluoro-D-deoxyglucose (FDG) in brain has allowed the measurement of cerebral utilization of exogenous glucose in man using positron computed tomography (PCT) and FDG. It is the goal of this study to use an isolated blood-perfused heart with physiologic perfusion and metabolic rate to develop and validate tracer kinetic models and operational equations of FDG and 11C-palmitate (CPA) as tracers for measurement of utilization of exogenous glucose and free fatty acids in myocardium. The FDG tracer kinetic model developed for brain will be first evaluated for its applicability in myocardium. Reformulation of model will be made if indicated from kinetic studies. Stability of the FDG method for estimating exogenous glucose utilization will be evaluated by measuring membrane transport and phosphorylation rate constants of glucose and FDG simultaneously. Rate constants of glucose will be obtained by 2-t-glucose, of which the tritium label is irreversibly lost to water after phosphorylation, thus isolating membrane transport and phosphorylation from other glycolytic reactions. Dual tracer experiments using FDG and 2-t-glucose will be performed under non-ischemic, ischemic and variable substrate conditions. Direct chemical assay of labeled compounds in tissue and effluent will be compared with those predicted by model for validation of the tracer kinetic approach. a preliminary model of CPA suggested from tracer kinetic studies in dog myocarcium will be investigated. Dual tracer experiments using C-14 and C-11 CPA will be performed to provide both tracer kinetic data (from C-11) and biochemical assay data (C-14) of labeled compounds in tissue and in effluent. Chemical assay data will be used to compare with predictions of the model for validation or reconfiguration of model. Experiments will be performed under various ischemic and substrate availability conditions to examine the stability and accuracy of the model. Practical operational equations for calculating myocardial utilization rates of exogenous glucose and FFA will be developed and optimized for their error sensitivities. Results obtained in this study will provide he necessary mathematical tool for quantifying myocardial metabolism studies in man with PCT.